This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The objective of this project is to determine the structural basis for the activation of the adenovirus proteinase (AVP) by its 11-amino-acid peptide cofactor (pVIc) using molecular dynamics simulations. Crystal structures of the inactive enzyme (AVP) and of the activated enzyme (AVP-pVIc) are known. Analysis of these structures indicates that upon the binding of pVIc to AVP activation may occur via a signal transduction pathway involving a series of contiguous structural changes. Molecular dynamics simulations will be used to determine the sequence of structural changes. In the future, the results of the molecular dynamics simulations will be used with structure-based drug design to obtain anti-viral agents.